Blood screening that accurately detected Down syndrome and other genetic fetal abnormalities in the first trimester could reduce the need for invasive testing with amniocentesis or chorionic villi sampling, researchers reported.
In a prospective study of nearly 1,000 British women, cell-free fetal DNA testing showed risk scores for each of trisomies 21, 18, and 13 were <0.01%, according to Kypros Nicolaides, MD, of the Harris Birthright Research Centre for Fetal Medicine at King's College London in England, and colleagues.
In another 11 cases, the risk score for trisomy 21 was >99% and for trisomies 18 and 13 was <0.01%, they wrote in Ultrasound in Obstetrics & Gynecology. In five cases, the risk score for trisomy 18 was >99% and the risk scores for trisomies 21 and 13 were <0.01%. In one case, the risk score for trisomy 13 was 34%, and the risk scores for trisomies 21 and 18 were <0.01%, the researchers stated.
The results are in line with those of another study published in early 2011 which showed that testing the mother's blood could rule out genetic abnormalities in the fetus.
Risk scores were calculated by combining the maternal serum concentrations of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin at 10 weeks with maternal age, previous history of trisomic pregnancy, and ultrasound findings at 12 weeks, the study stated.
Chorionic villi sampling was conducted in 16 of 17 cases with a high-risk score for aneuploidies from the cell-free DNA testing. In 15 suspect cases, cytogenetic analysis confirmed abnormality.
Testing done in 1,005 pregnancies at 10 weeks had a lower false-positive rate and higher sensitivity for fetal trisomy than the combined test that was conducted between 11 and 13 weeks of pregnancy via ultrasound and hormonal analysis of the mother's blood, the study stated.
Both cell-free fetal DNA and combined testing detected all trisomies, but the estimated false-positive rates were 0.1% and 3.4%, respectively.
Over 7 months, women in their 10th and 12th week of gestation who were getting healthcare at the London hospital were studied. Blood samples taken at 10 weeks' gestation were sent to the U.S. for analysis and results were returned in time for the 12-week checkup. Parents were advised to consider fetal karyotyping by chorionic villi sampling if results indicated a high risk for trisomies 21, 18, or 13.
The median maternal age was 36.7 (20.4 to 48.8) years, the median maternal weight was 62.4 kg (137.5 lbs) kg and the median crown-rump length at sampling was 38 mm (32 to 45 mm). Most women were Caucasian (900, or 89.5%). Conception was spontaneous in 861 (85.7%), by in-vitro fertilization in 117 (11.6%) and after ovulation drugs in 27 (2.7%).
The study did not diagnose aneuploidies other than trisomies 21, 18, and 13, the authors stated.
In a corresponding study published online simultaneously, Nicolaides and colleagues also found that the serum screening contingent on the combined test at 11 to 13 weeks detected 98% of cases, with invasive testing necessary in less than 0.5% of cases.
That second study analyzed pregnancies at three U.K. hospitals between March 2006 and May 2012, defining risk cutoffs with corresponding detection and false-positive rates for trisomy 21 exclusively. The authors said the second study was limited to the prediction of trisomy 21 because it has been the main factor in defining strategies of screening for aneuploidies, and because doing so minimized the complexity of the model.
"The results demonstrate that in contingent screening, a detection rate of 98% in fetuses with trisomy 21, at an overall invasive testing rate <0.5%, could be achieved by offering the cell-free DNA test to about 36%, 21%, and 11% of cases identified by first-line screening using the combined test alone, using the combined test with the addition of serum placental growth factor (PIGF) and alpha-fetoprotein (AFP), and using the combined test with the addition of PIGF, AFP, and ductus venosus pulsatility index for veins, respectively," the authors wrote.
"Screening for trisomy 21 by [cell-free] DNA testing contingent on the results of an expanded combined test would retain the advantages of the current method of screening, but with a simultaneous major increase in detection rate and decrease in the rate of invasive testing," they concluded.
The studies were funded by a grant from the Fetal Medicine Foundation.
Disclosures for the authors were not available at press time.
- Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Ultrasound in Obstetrics & GynecologySource Reference: Nicolaides KH, et al "Implementation of maternal blood cell-free DNA testing in early screening for aneuploides" Ultrasound Obstet Gynecol 2013; DOI: 10.1002/uog.12504.
Ultrasound in Obstetrics & GynecologySource Reference: Nicolaides KH, et al "First-trimester contingent screening for trisomy 21 by biomarkers and maternal blood cell-free DNA testing" Ultrasound Obstet Gynecol 2013; DOI: 10.1002/uog.12511.